COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME … · 2014. 7. 17. ·...

COLD SPRING HARBOR SYMPOSIAON QUANTITATIVE BIOLOGY

VOLUME LXXVIII

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COLD SPRING HARBOR SYMPOSIAON QUANTITATIVE BIOLOGY

VOLUME LXXVIII

Immunity and Tolerance

symposium.cshlp.org

Symposium organizers and Proceedings editors: Anne O’Garra (MRC National Institutefor Medical Research, London), Michel Nussenzweig (HHMI/The Rockefeller University, New York),

Stephen Smale (University of California, Los Angeles), and David Stewart and Bruce Stillman(Cold Spring Harbor Laboratory)

COLD SPRING HARBOR LABORATORY PRESS

2013




COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME LXXVIII

# 2013 by Cold Spring Harbor Laboratory PressInternational Standard Book Number 978-1-621820-84-0 (cloth)

International Standard Book Number 978-1-621820-85-7 (paper)

International Standard Serial Number 0091-7451

Library of Congress Catalog Card Number 34-8174

Printed in the United States of America

All rights reserved

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

Founded in 1933 by

REGINALD G. HARRIS

Director of the Biological Laboratory 1924 to 1936

Previous Symposia Volumes

I (1933) Surface Phenomena

II (1934) Aspects of Growth

III (1935) Photochemical Reactions

IV (1936) Excitation Phenomena

V (1937) Internal Secretions

VI (1938) Protein Chemistry

VII (1939) Biological Oxidations

VIII (1940) Permeability and the Nature of Cell Membranes

IX (1941) Genes and Chromosomes: Structure and Organization

X (1942) The Relation of Hormones to Development

XI (1946) Heredity and Variation in Microorganisms

XII (1947) Nucleic Acids and Nucleoproteins

XIII (1948) Biological Applications of Tracer Elements

XIV (1949) Amino Acids and Proteins

XV (1950) Origin and Evolution of Man

XVI (1951) Genes and Mutations

XVII (1952) The Neuron

XVIII (1953) Viruses

XIX (1954) The Mammalian Fetus: Physiological Aspects of

Development

XX (1955) Population Genetics: The Nature and Causes of Genetic

Variability in Population

XXI (1956) Genetic Mechanisms: Structure and Function

XXII (1957) Population Studies: Animal Ecology and Demography

XXIII (1958) Exchange of Genetic Material: Mechanism and

Consequences

XXIV (1959) Genetics and Twentieth Century Darwinism

XXV (1960) Biological Clocks

XXVI (1961) Cellular Regulatory Mechanisms

XXVII (1962) Basic Mechanisms in Animal Virus Biology

XXVIII (1963) Synthesis and Structure of Macromolecules

XXIX (1964) Human Genetics

XXX (1965) Sensory Receptors

XXXI (1966) The Genetic Code

XXXII (1967) Antibodies

XXXIII (1968) Replication of DNA in Microorganisms

XXXIV (1969) The Mechanism of Protein Synthesis

XXXV (1970) Transcription of Genetic Material

XXXVI (1971) Structure and Function of Proteins at the

Three-Dimensional Level

XXXVII (1972) The Mechanism of Muscle Contraction

XXXVIII (1973) Chromosome Structure and Function

XXXIX (1974) Tumor Viruses

XL (1975) The Synapse

XLI (1976) Origins of Lymphocyte Diversity

XLII (1977) Chromatin

XLIII (1978) DNA: Replication and Recombination

XLIV (1979) Viral Oncogenes

XLV (1980) Movable Genetic Elements

XLVI (1981) Organization of the Cytoplasm

XLVII (1982) Structures of DNA

XLVIII (1983) Molecular Neurobiology

XLIX (1984) Recombination at the DNA Level

L (1985) Molecular Biology of Development

LI (1986) Molecular Biology of Homo sapiens

LII (1987) Evolution of Catalytic Function

LIII (1988) Molecular Biology of Signal Transduction

LIV (1989) Immunological Recognition

LV (1990) The Brain

LVI (1991) The Cell Cycle

LVII (1992) The Cell Surface

LVIII (1993) DNA and Chromosomes

LVIX (1994) The Molecular Genetics of Cancer

LX (1995) Protein Kinesis: The Dynamics of Protein Trafficking and

Stability

LXI (1996) Function & Dysfunction in the Nervous System

LXII (1997) Pattern Formation during Development

LXIII (1998) Mechanisms of Transcription

LXIV (1999) Signaling and Gene Expression in the Immune

System

LXV (2000) Biological Responses to DNA Damage

LXVI (2001) The Ribosome

LXVII (2002) The Cardiovascular System

LXVIII (2003) The Genome of Homo sapiens

LXIX (2004) Epigenetics

LXX (2005) Molecular Approaches to Controlling Cancer

LXXI (2006) Regulatory RNAs

LXXII (2007) Clocks and Rhythms

LXXIII (2008) Control and Regulation of Stem Cells

LXXIV (2009) Evolution: The Molecular Landscape

LXXV (2010) Nuclear Organization and Function

LXXVI (2011) Metabolism and Disease

LXXVII (2012) The Biology of Plants

Front cover ( paperback): Images by James Duffy and James Whitaker, Cold Spring Harbor Laboratory.

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Website access: Please visit our companion website at symposium.cshlp.org. For access questions or problems, please contact Kathy Cirone,CSHL Press Subscription Manager, at [email protected].




Symposium Participants

AGUIRRE, DANIELLE, University of Rhode Island, Providence

AHMED, ALYSIA, California Institute of Technology, Pasadena

AHMED, RAFI, Emory University School of Medicine, Atlanta, Georgia

AHN, EUNSEON, Emory University, Atlanta, Georgia

AKIRA, SHIZUO, Osaka University, Suita, Osaka, Japan

AKONDY, RAMA, Emory University, Atlanta, Georgia

ALLEN, HAMISH, Abbvie Bioresearch Center, Worcester, Massachusetts

ALLISON, JAMES, UT MD Anderson Cancer Center, Houston, Texas

ALMEIDA, ANA, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

ALONZO, ERIC, Massachusetts General Hospital/Harvard, Charlestown

ALT, FREDERICK, HHMI/Children’s Hospital, Boston, Massachusetts

AMSEN, DERK, Sanquin Blood Research, Amsterdam, The Netherlands

ANDRES-TERRE, MARTA, Cold Spring Harbor Laboratory, Cold Spring

Harbor, New York

APPS, RICHARD, SAIC Frederick, Frederick, Maryland

ARENZANA, TERESITA, University of California at Los Angeles

ARVEY, AARON, Memorial Sloan-Kettering Cancer Center, New York,

New York

ASTRY, BRIAN, University of Maryland School of Medicine, Baltimore

AVILA, CECILIA, Stony Brook University, Stony Brook, New York

BAILIS, WILL, University of Pennsylvania, Philadelphia

BALAZS, ALEJANDRO, California Institute of Technology, Pasadena, Cali-

fornia

BALTIMORE, DAVID, California Institute of Technology, Pasadena

BANERJEE, DALIYA, BiogenIdec, Cambridge, Massachusetts

BAR-ON, LIAT, IIBR, Ness-Ziona, Israel

BARRY, KEVIN, University of California, Berkeley

BARTHELS, CHRISTIAN, Ludwig Maximillian University, Munich, Ger-

many

BASSO, CAMILLA, Institute for Research in Biomedicine, Bellinzona,

Switzerland

BASU, UTTIYA, Columbia University, New York, New York

BELKAID, YASMINE, National Institute of Allergy and Infectious Diseases,

Bethesda, Maryland

BENDELAC, ALBERT, University of Chicago, Chicago, Illinois

BENOIST, CHRISTOPHE, Harvard Medical School, Boston, Massachusetts

BEN-SASSON, ZAMI, Hebrew University Medical School, Jerusalem, Je-

rusalem, Israel

BERBERICH-SIEBELT, FRIEDERIKE, University of Würzburg, Würzburg,

Germany

BERGMANN, JAN, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

BEZBRADICA, JELENA, Yale University, New Haven, Connecticut

BJORKMAN, PAMELA, California Institute of Technology/HHMI, Pasa-

dena

BLANKENHAUS, BIRTE, Instituto Gulbenkian de Ciencia, Oeiras, Portugal

BLISKA, JAMES, Stony Brook University, Stony Brook, New York

BLISS, CARLY, The Jenner Institute, Oxford, United Kingdom

BOLTON, HOLLY, Centenary Institute, Camperdown, Australia

BRIEN, JAMES, Washington University, St. Louis, Missouri

BUDZYNSKA, PAULINA, University of Turku, Turku, Finland

BURKLY, LINDA, Biogen Idec, Cambridge, Massachusetts

BURZYN, DALIA, Harvard University, Boston, Massachusetts

BUSSLINGER, MEINRAD, Research Institute of Molecular Pathology, Vi-

enna, Austria

CANTRELL, DOREEN, College of Life Sciences Dundee, United Kingdom

CARPINO, NICK, SUNY Stony Brook, Stony Brook, New York

CASANOVA, JEAN-LAURENT, The Rockefeller University, New York, New

York

CASELLAS, RAFAEL, NIH–NIAMS, Bethesda, Maryland

CEMERSKI, SASO, Bristol-Myers Squibb, Princeton, New Jersey

CHAEMSAITHONG, PIYA, Perinatology Research Branch/Wayne State Uni-

versity, Detroit, Michigan

CHAHWAN, RICHARD, Albert Einstein College of Medicine, Bronx, New

York

CHANG, ABRAHAM, Genentech, South San Francisco, California

CHANG, JIHOON, MGH/HMS, Charlestown, Massachusetts

CHAUHAN, ANIL, Saint Louis University, Saint Louis, Missouri

CHAVARRIA-SMITH, JOSEPH, University of California, Berkeley

CHAWLA, AJAY, University of California, San Francisco

CHEN, DIANA, MGH, Harvard Medical School, Boston, Massachusetts

CHEN, WANJUN, NIDCR, NIH, Bethesda, Maryland

CHENG, LIANG, University of North Carolina at Chapel Hill

CHI, HONGBO, St. Jude Children’s Research Hospital, Memphis, Ten-

nessee

CHOI, HEE JUNE, Pohang University of Science and Technology, Pohang,

South Korea

CHONG, MARK, St Vincent’s Institute, Fitzroy, Australia

CHUNG, LAWTON, Stony Brook University, Stony Brook, New York

CIENIEWICZ, BRANDON, Stony Brook University, Stony Brook, New York

CIHAKOVA, DANIELA, Johns Hopkins University, Baltimore, Maryland

COHEN, TAYLOR, Columbia University, New York, New York

COLGAN, JOHN, University of Iowa, Iowa City

CONLAN, THOMAS, UCL, London, United Kingdom

COOK, SARAH, The University of Birmingham, Birmingham, United

Kingdom

COOPER, CATHLEEN, National Institutes of Health, Bethesda, Maryland

COOPER, MAX, Emory University, Atlanta, Georgia

CORDANI, GERALD, North Shore Medical, Huntington, New York

CRESSWELL, PETER, HHMI/Yale University School of Medicine, New

Haven, Connecticut

CROTTY, SHANE, La Jolla Institute for Allergy and Immunology, La Jolla,

California

DAVIS, MARK, HHMI, Stanford University School of Medicine, Stanford,

California

DE OBALDIA, ELLEN, University of Pennsylvania, Philadelphia

DEMPSEY, LAURIE, Nature Immunology, Jersey City, New Jersey

DI NOIA, JAVIER, Institut de Recherche Cliniques de Montréal, Montréal,

Canada

DIETZ, LENA, University of Würzburg, Würzburg, Germany

DINER, ELIE, University of California at Berkeley

DING, ZHIHU (Jeff ), Sanofi, Cambridge, Massachusetts

DOBENECKER, MARC-WERNER, The Rockefeller University, New York,

New York

DOEDEE, ANNE, RIVM, Bilthoven, The Netherlands

DONG, QIWEN, Stony Brook University, Stony Brook, New York

DOODY, JACQUELINE, ImClone Systems, New York, New York

DOUGLASS Jr, EUGENE, Yale University, New Haven, Connecticut

DUMSTREI, KARIN, The EMBO Journal, Heidelberg, Germany

EISENÄCHER, KATHARINA, Technical University Munich, Germany

ESPAILLAT, MEL PILAR, Stony Brook University, Stony Brook, New York

FEDOROV, VICTOR, Tri-Institutional MSTP Program, New York, New

York

FEENEY, ANN, The Scripps Research Institute, La Jolla, California

FELIX, NATHAN, Bristol-Myers Squibb, Princeton, New Jersey

FLACH, HENRIK, University of California at San Francisco

FLAVELL, MADLYN, Guilford, Connecticut

FLAVELL, RICHARD, Yale University School of Medicine, New Haven,

Connecticut

FLORSHEIM, ESTHER, University of Sao Paulo, Sao Paulo, Brazil

FONTENOT, JASON, Biogen Idec, Cambridge, Massachusetts

v




FOREMAN, HUI-CHEN, Stony Brook University, Stony Brook, New York

FRANCIS, DAILIA, Icahn School of Medicine at Mount Sinai, New York,

New York

FU, WENXIAN, Harvard Medical School, Boston, Massachusetts

FUJII, SHIN-ICHIRO, RIKEN, IMS, Yokohama, Japan

FUKUTO, HANA, Stony Brook University, Stony Brook, New York

GALIMIDI, RACHEL, California Institute of Technology, Pasadena

GAO, YAN, Yale University, New Haven, Connecticut

GARCIA, GABRIELLE, Tufts University School of Medicine, Boston, Mas-

sachusetts

GARRARD, WILLIAM, University of Texas Southwestern Medical Center,

Dallas

GASSER, STEPHAN, National University of Singapore, Singapore

GASTEIGER, GEORG, Memorial Sloan-Kettering Cancer Center, New

York, New York

GEARHART, PATRICIA, National Institute on Aging, NIH, Baltimore,

Maryland

GEISSMANN, FREDERIC, Centre for Molecular & Cellular Biology of In-

flammation, London, United Kingdom

GHOSH, SANKAR, Columbia University College of Physicians & Sur-

geons, New York, New York

GHOSN, ELIVER, Stanford University School of Medicine, Stanford,

California

GOREVIC, PETER, Mount Sinai School of Medicine, New York, New York

GOVENDER, UMESHREE, Institut Pasteur, Paris, France

GRACA, LUIS, Instituto de Medicina Molecular Lisbon, Lisbon, Portugal

GRODZICKER, TERRI, Cold Spring Harbor Laboratory, Cold Spring Har-

bor, New York

GROSSCHEDL, RUDOLF, Max Planck Institute of Immunobiology & Epi-

genetics, Freiburg, Germany

GROTENBREG, GIJSBERT, National University of Singapore, Singapore

GRUBER, SABINE, University Cologne, Cologne, Germany

GUREVICH, IRINA, Weizmann Institute, Rehovot, Israel

HALE, SCOTT, Emory University, Atlanta, Georgia

HALPERIN, REBECCA, Boston University School of Medicine, Boston,

Massachusetts

HAN, ARNOLD, Stanford University, Los Altos Hills, California

HARRISON, OLIVER, University of Oxford, Oxford, United Kingdom

HASHIMOTO, TAKASHI, Kurume University School of Medicine, Kurume,

Fukuoka, Japan

HEDRICK, STEPHEN, University of California, San Diego, La Jolla

HEGER, KLAUS, Max Planck Institute of Biochemistry, Martinsried,

Germany

HEINONEN, MIRKKA, University of Turku, Turku, Finland

HEISEKE, ALEXANDER, Technical University Munich, Munich, Germany

HINTERBERGER, MARIA, Ludwig Maximillian University, Munich, Ger-

many

HITCHCOCK, JESSICA, University of Birmingham, Birmingham, United

Kingdom

HO, TING HIN, The University of Hong Kong, Hong Kong

HSU, LIH-YUN, University of California at San Francisco

HU, BO, Yale University, New Haven, Connecticut

IMANISHI-KARI, THEREZA, Tufts University, School of Medicine, Boston,

Massachusetts

INGLIS, JOHN, Cold Spring Harbor Laboratory Press, Woodbury, New

York

IVANOV, MAYA, Stony Brook University, Stony Brook, New York

JACOBS, JR, WILLIAM, Albert Einstein College of Medicine/HHMI,

Bronx, New York

JAECKEL, ELMAR, Hannover Medical School, Hannover, Germany

JAKIMO, ALAN, Hofstra University, Hempstead, New York

JENQ, ROBERT, Memorial Sloan-Kettering Cancer Center, New York,

New York

JIANG, NING, The University of Texas at Austin

JIN, CHENGCHENG, Yale University, New Haven, Connecticut

JINUSHI, MASAHISA, Hokkaido University, Sapporo, Japan

KACZMAREK, LEONARD, Yale University, New Haven, Connecticut

KAMPHORST, ALICE, Emory University, Atlanta, Georgia

KAPPLER, JOHN, HHMI/National Jewish Center, Denver, Colorado

KASHKOULI, SHIRIN, Stony Brook University, Stony Brook, New York

KENNEDY, WILLIAM DEXTER, Genentech, San Francisco, California

KENTER, AMY, University of Illinois College of Medicine, Chicago

KIEFFER-KWON, Kyongrim, NIH, Bethesda, Maryland

KIM, HYE-JUNG, Dana Farber Cancer Institute, Boston, Massachusetts

KIM, SANGWON, New York University School of Medicine, New York

KINJYO, ICHIKO, Centenary Institute, Sydney, Australia

KISHIMOTO, TAKASHI, Selecta Biosciences, Watertown, Massachusetts

KISIELOW, JAN, ETH Zürich, Zürich, Switzerland

KOFF, WAYNE, International AIDS Vaccine Initiative, New York, New

York

KORN, THOMAS, Technische Universität München, Munich, Germany

KRETZER, NICOLE, Washington University School of Medicine, St. Louis,

Missouri

KRUG, LAURIE, Stony Brook University, Stony Brook, New York

KUMAR, RAJNISH, New York University School of Medicine, New York

KUMARAN, R. ILENG, Cold Spring Harbor Laboratory, Cold Spring Har-

bor, New York

KURACHI, MAKOTO, University of Pennsylvania, Philadelphia

KURSCHUS, FLORIAN, University Medical Center of the Johannes Gut-

enberg, Mainz, Germany

KWAK, SANG-MIN, Gwang-ju Institute of Science and Technology, Gwang-

ju, South Korea

KYEWSKI, BRUNO, German Cancer Research Center, Heidelberg, Ger-

many

KYLUIK-PRICE, DANA, Canadian Blood Services, University of British

Columbia, Vancouver, Canada

LAHESMAA, RIITTA, University of Turku, Turku, Finland

LAKY, KAREN, NIH, Bethesda, Maryland

LAM, RUNYI ADELINE, National University of Singapore, Singapore

LEONARD, WARREN, HHS/NIH/NHLBI, Bethesda, Maryland

LEVERRIER, YANN, INSERM, Lyon, France

LIAO, WEI, National Institutes of Health, Bethesda, Maryland

LIFKE, ALEXANDER, Roche Diagnostics GmbH, Penzberg, Germany

LIN, JIAN-XIN, NHLBI/NIH, Bethesda, Maryland

LIN, YANG-DING, Penn State University, University Park, Pennsylvania

LITTMAN, DAN, New York University School of Medicine and HHMI,

New York

LIU, HONG-HSING, National Health Research Institutes, Zhunan Town,

Miaoli County, Taiwan

LOCKSLEY, RICHARD, University of California at San Francisco

LOYTER, ABRAHAM, Hebrew University of Jerusalem, Israel

LUCAS, CARRIE, NIAID/NIH, Bethesda, Maryland

LUM, JENIFER, Crucell Holland B.V., Leiden, The Netherlands

MACCARTHY, THOMAS, Stony Brook University, Stony Brook, New York

MADI, ASAF, Weizmann Institute of Science, Rehovot, Israel

MAK, TAK, Ontario Cancer Institute, Toronto, Canada

MALIREDDI, R.K. SUBBARAO, St. Jude Children’s Research Hospital,

Memphis, Tennessee

MAO, YUMENG, Karolinska Institutet, Stockholm, Sweden

MARCUS, EMILIE, Cell Press, Cambridge, Massachusetts

MARRACK, PHILIPPA, HHMI/National Jewish Center, Denver, Colorado

MASANI, SHAHNAZ, Michigan State University, East Lansing

MATHIS, DIANE, Harvard Medical School, Boston, Massachusetts

MCLAUGHLIN, PATRICK, Stony Brook University, Stony Brook, New

York

MEDZHITOV, RUSLAN, HHMI / Yale University, New Haven, Connecticut

MEHTA, ARNAV, California Institute of Technology, Pasadena

MERAD, MIRIAM, The Mount Sinai Hospital School of Medicine, New

York, New York

MEREDITH, MATTHEW, Harvard Medical School, Boston, Massachusetts

METZENBERG, STAN, California State University, Northridge, California

MICHEL, FREDRIQUE, Institut Pasteur, Paris, France

MILCAREK, CHRISTINE, University of Pittsburgh, Pittsburgh, Pennsyl-

vania

MILLER, LOUIS, NIAID, NIH, Rockville, Maryland

MILLER, MARINA, University of California, San Diego

MISAWA, TAKUMA, Osaka University, Suita, Japan

MOITA, LUIS, Instituto de Medicina Molecular, Lisboa, Portugal

MULJO, STEFAN, National Institutes of Health, NIAID, Bethesda,

Maryland

MÜLLER, ELISABETH, University of Oslo, Oslo, Norway

MURPHY, KENNETH, HHMI/Washington University, St. Louis, Missouri

MURRE, CORNELIS, University of California, San Diego, La Jolla

NAIR, PRIYANKA, Mount Sinai School of Medicine, New York, New

York

NATOLI, GIOACCHINO, European Institute of Oncology, Milan, Italy

SYMPOSIUM PARTICIPANTSvi




NEDOSPASOV, SERGEI, Engelhardt Institute of Molecular Biology, Mos-

cow, Russia

NEWMAN, REBECCA, Babraham Institute, Cambridge, United Kingdom

NOUBADE, RAJKUMAR, Genentech, South San Francisco, California

NUSSENZWEIG, MICHEL, HHMI/The Rockefeller University, New York,New York

OBST, REINHARD, University of Munich, Munich, Germany

OCHIAI, KYOKO, Tohoku University, Sendai, Japan

O’GARRA, ANNE, MRC National Institute for Medical Research, London,

United Kingdom

OLDENBURG, MARINA, Universitätsklinkikum Essen, Essen, Germany

ONG, SUFEY, Johns Hopkins University, Baltimore, Maryland

ORTIZ, BENJAMIN, City University of New York, Hunter College, New

York, New York

PAMER, ERIC, Memorial Sloan-Kettering Cancer Center, New York, New

York

PARK, SUNG-KYUN, University of Texas Southwestern Medical Center,

Dallas

PARVEEN, NAZIA, Centre for DNA Fingerprinting and Diagnostics, Hy-

derabad, India

PASCUAL, M. VIRGINIA, Baylor Institute for Immunology Research, Dal-

las, Texas

PASMAN, LESLEY, Yale University, New Haven, Connecticut

PATEL, SONAL, California Institute of Technology, Pasadena

PAUL, WILLIAM, National Institutes of Health, NIAID, Bethesda, Mary-

land

PERCHER, AVITAL, The Rockefeller University, New York, New York

PHILBRICK, WILLIAM, Yale University School of Medicine, New Haven,

Connecticut

PIERCE, SUSAN, NIAID, NIH, Rockville, Maryland

PINTO, AMELIA, Washington University School of Medicine, Saint Louis,

Missouri

PLOEGH, HIDDE, Whitehead Institute for Biomedical Research, Cam-

bridge, Massachusetts

POLTORAK, ALEXANDER, Tufts University, Boston, Massachusetts

POPE, SCOTT, Yale University, New Haven, Connecticut

POWELL, JONATHAN, Johns Hopkins University School of Medicine, Bal-

timore, Maryland

POWRIE, FIONA, University of Oxford, Oxford, United Kingdom

PRINJHA, RAB, GlaxoSmithKline, Stevenage, United Kingdom

QI, HAI, Tsinghua University, Beijing, China

QIAN, JASON, NIH, Bethesda, Maryland

QIU, JIN, Tufts University, Boston, Massachusetts

QUANN, EMILY, Cell Signaling Technology, Danvers, Massachusetts

RADA, CRISTINA, MRC Laboratory of Molecular Biology, Cambridge,

United Kingdom

RAJEWSKY, KLAUS, Max Delbruck Center for Molecular Medicine, Ber-

lin, Germany

RAMAKRISHNAN, LALITA, University of Washington, Seattle

RAMOS, SUSANA, Fundação Gulbenkian - IGC, Oeiras, Portugal

RAMSDELL, FRED, Novo Nordisk, Seattle, Washington

RAO, ANJANA, La Jolla Institute for Allergy & Immunology, La Jolla,

California

RAO, SHEILA, University of Pennsylvania, Philadelphia

RATTAY, KRISTIN, German Cancer Research Center, Heidelberg, Germany

RAUF, PHILIPP, MPI of Immunobiology and Epigenetics, Freiburg, Ger-

many

RAULET, DAVID, University of California, Berkeley

RAVETCH, JEFFREY, The Rockefeller University, New York, New York

REICH, NANCY, Stony Brook University, Stony Brook, New York

RIBECHINI, ELIANA, University of Würzburg, Würzburg, Germany

RICHARD, GUYLDA, Farmingdale State College, Farmingdale, New York

ROCHMAN, YRINA, Cincinnati Children’s Hospital, Cincinnati, Ohio

ROMANOV, GALINA, Stony Brook University, Stony Brook, New York

ROSENGREN, SANNA, Halozyme Therapeutics, Inc., San Diego, California

ROTH, SUSANNE, Technical University Munich, Munich, Germany

ROTHENBERG, ELLEN, California Institute of Technology, Pasadena

RUDENSKY, ALEXANDER, Memorial Sloan-Kettering Cancer Center, New

York, New York

RUSSELL, LISA, National Institute on Aging, NIH, Baltimore, Maryland

RUSSO, MOMTCHILO, University of São Paulo, São Paulo, Brazil

RUTZ, SASCHA, Genentech, South San Francisco, California

RYBAKIN, VASILY, The Scripps Research Institute, San Diego, California

SALLUSTO, FEDERICA, Institute for Research in Biomedicine, Bellinzona,

Switzerland

SALOMON, BENOIT, INSERM, Paris, France

SANSOM, DAVID, University College London, London, United Kingdom

SANTANA, ALEXIS, Stony Brook University, Stony Brook, New York

SANTIAGO-SCHWARZ, FRANCES, Farmingdale State College, Farmingdale,

New York

SAPOZNIKOV, ANITA, Weizmann Institute, Shoham, Israel

SCHAEFER, ANNE, Mt. Sinai School of Medicine, New York, New York

SCHARF, LOUISE, California Institute of Technology, Pasadena

SCHATZ, DAVID, HHMI/Yale Medical School, New Haven, Connecticut

SCHAUE, DORTHE, University of California at Los Angeles

SCHEIBLE, KRISTIN, University of Rochester, Rochester, New York

SCHREIBER, ROBERT, Washington University School of Medicine, St.

Louis, Missouri

SCHROEFELBAUER, BAERBEL, Molecular Cell, Cambridge, Massachusetts

SCHWARTZBERG, PAMELA, NIH, Bethesda, Maryland

SCHWICKERT, TANJA, IMP, Vienna, Austria

SEVER, RICHARD, Cold Spring Harbor Laboratory Press, Cold Spring

Harbor, New York

SHALABY, KARIM, McGill University, Montreal, Canada

SHARMA, RAKHI, Toronto Western Research Institute, Toronto, Canada

SHI, JUNWEI, Cold Spring Harbor Laboratory, Cold Spring Harbor, New

York

SIDDLE, HANNAH, University of Cambridge, Cambridge, United King-

dom

SIGMUND, ANNA, University Hospital Essen, Essen, Germany

SINGH, HARINDER, Genentech, South San Francisco, California

SISIRAK, VANJA, Columbia University, New York, New York

SIVAKUMARAN, SHIVAJANANI, University College London Cancer Institute,

London, United Kingdom

SKOK, JANE, New York University School of Medicine, New York

SKOWYRA, DOROTA, St. Louis University School of Medicine, St. Louis,

Missouri

SMALE, STEPHEN, University of California at Los Angeles School of

Medicine, Los Angeles

SMITH, MELANIE, University of California at San Francisco

SMITH, RACHEL, Life Technologies, Eugene, Oregon

SOHN, HAE WON, NIAID/NIH, Rockville, Maryland

SON, MYOUNGSUN, The Feinstein Institute for Medical Research, Man-

hasset, New York

SONG, ZHILI, Sanofi, Cambridge, Massachusetts

SPECTOR, DAVID, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

SRINIVASAN, NAREN, University of Oxford, Oxford, United Kingdom

STAROSVETSKY, ELINA, Technion, Technion Haifa, Israel

STAVNEZER, JANET, University of Massachusetts Medical School,

Worcester

STEWART, DAVID, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

STEWART, SAM, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

STILLMAN, BRUCE, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

STORCK, SEBASTIEN, INSERM U783 Universite Paris Descartes, Paris,

France

STRID, TOBIAS, Experimental Hematology/Linköping University, Linkö-

ping, Sweden

SUN, XIAO-HONG, Oklahoma Medical Research Foundation, Oklahoma

City

SWICK, ADAM, University of Wisconsin at Madison

TALIB, SOHEL, California Institute for Regenerative Medicine, San Fran-

cisco

TAM, JASON, Stony Brook University, Stony Brook, New York

TANAKA, ATSUSHI, Osaka University, Suita, Osaka, Japan

TANIGUCHI, TADATSUGU, University of Tokyo, Tokyo, Japan

TANIUCHI, ICHIRO, RIKEN, IMS-RCAI, Yokohama, Japan

TAO, PAN, The Catholic University of America, Washington, District of

Columbia

TARAKHOVSKY, ALEXANDER, The Rockefeller University, New York,

New York

TARTEY, SARANG, Institute for Virus Research, Kyoto University, Kyoto,

Japan

SYMPOSIUM PARTICIPANTS vii




TASDOGAN, ALPASLAN, University of Ulm, Ulm, Germany

THOMPSON, CRAIG, Memorial Sloan-Kettering Cancer Center, New York,

New York

THOMPSON, LIZ, Immunity, Cambridge, Massachusetts

TONG, ANN-JAY, University of California at Los Angeles

TORRES, ANNMARIE, Stony Brook University, Stony Brook, New York

TRIFARI, SARA, La Jolla Institute for Allergy and Immunology, La Jolla,

California

TRINATH, JAMMA, Indian Institute of Science, Bangalore, India

TRIPATHI, SUBHASH, Turku Centre for Biotechnology, Turku, Finland

TSAGARATOU, AGELIKI, La Jolla Institute for Allergy & Immunology, La

Jolla, California

TSUIJI, MAKOTO, Hoshi University, Tokyo, Japan

UNGERBÄCK, JONAS, Experimental Hematology/Linköping University,

Linköping, Sweden

VAETH, MARTIN, University of Würzburg, Würzburg, Germany

VAKNIN, ILAN, Compugen Ltd., Tel Aviv, Israel

vAN DEN HAM, HENK-JAN, Erasmus Medical Center, Rotterdam,

Netherlands

VAN DER VEEN, ANNEMARTHE, Cancer Research UK London Research

Institute, London, United Kingdom

VEROMAA, TIMO, Biotie Therapies Corp., Turku, Finland

VICTORA, GABRIEL, Whitehead Institute for Biomedical Research, Cam-

bridge, Massachusetts

VINUESA, CAROLA, Australian National University, Canberra City, Aus-

tralia

vON BOEHMER, HARALD, Dana-Farber Cancer Institute, Boston, Massa-

chusetts

WAISMAN, ARI, University Mainz, Mainz, Germany

WALKER, BRUCE, The Ragon Institute of Massachusetts General Hospi-

tal, Massachusetts Institute of Technology and Harvard, Cambridge,

Massachusetts

WALTER, GINA, King’s College London, London, United Kingdom

WAN, YISONG, University of North Carolina at Chapel Hill

WANG, FENG, Stanford University, Stanford, California

WANG, HAOPENG, University of California at San Francisco

WANG, JING, NIH, Rockville, Maryland

WANG, LIN, GlaxoSmithKline Pharmaceuticals, Inc., Collegeville, Penn-

sylvania

WANG, WEI-BEI, National Health Research Institutes, Miaoli County,

Taiwan

WANG, XIAOYING, Stony Brook University, Stony Brook, New York

WARDEMANN, HEDDA, Max Planck Institute for Infection Biology, Berlin,

Germany

WEBB, CAROL, Oklahoma Medical Research Foundation, Oklahoma City

WEGIEL, BARBARA, Harvard Medical School/BIDMC, Boston, Massa-

chusetts

WEISS, ART, HHMI/UCSF, San Francisco, California

WEISS, URSULA, Nature Magazine, London, United Kingdom

WEISSMAN, IRVING, Stanford University, Stanford, California

WERMELING, FREDRIK, The Rockefeller University, New York, New

York

WESEMANN, DUANE, Harvard Medical School, Boston, Massachusetts

WHICHER, CHARLOTTE, MRC NIMR, London, United Kingdom

WICHROSKI, MICHAEL, Bristol-Myers Squibb, Wallingford, Connecticut

WITKOWSKI, JAN, Cold Spring Harbor Laboratory, Cold Spring Harbor,

New York

WOLSKI, DAVID, Massachusetts General Hospital, Boston

WRAMMERT, JENS, Emory University, Atlanta, Georgia

WU, TUOQI, Emory University, Atlanta, Georgia

XIAO, CHANGCHU, The Scripps Research Institute, La Jolla, California

XIONG, NA, The Pennsylvania State University, University Park

YAMAZAKI, SAYURI, Nagoya City University, Nagoya, Japan

YAN, CATHERINE, Beth Israel Deaconess Medical Center, Boston, Mas-

sachusetts

YANG, KAI, St Jude Children’s Research Hospital, Memphis, Tennessee

YOKOYAMA, WAYNE, HHMI/Washington University, St. Louis, Missouri

YOSHIMOTO, TOMOHIRO, Hyogo College of Medicine, Nishinomiya,

Japan

YOUNGBLOOD, BEN, Emory University, Atlanta, Georgia

YU, XIAOFEI, University of Texas Southwestern Medical Center, Dallas

YUAN, CHAOHUI, Stony Brook University, Stony Brook, New York

ZANG, XINGXING, Albert Einstein College of Medicine, Bronx, New

York

ZANOTTI, KIMBERLY, National Institutes of Health, Baltimore, Maryland

ZHANG, RUAN, Massachusetts General Hospital, Charlestown, Massa-

chusetts

ZHANG, YUE, Stony Brook University, Stony Brook, New York

ZHAO, FAN, Brandeis University, Waltham, Massachusetts

ZHAO, LIJUAN, Children’s Hospital Boston, Massachusetts

ZHU, JINFANG, NIAID, National Institutes of Health, Bethesda, Mary-

land

SYMPOSIUM PARTICIPANTSviii




Row 1: Z. Ben-Sasson, P. Marrack; T. Taniguchi, D. Stewart; A. Tarakhovsky, A. Schaefer

Row 2: B. Blankenhaus, S. Ramos; H.-J. Kim, J. Chang

Row 3: Wine and cheese party at Airslie

Row 4: J. Ravetch, D. Raulet; E. Ribechini, H.-J. van den Ham; W. Jacobs, Jr, W.D. Kennedy ix




Row 1: J.D. Watson, M. Nussenzweig, W. Yokoyama; J. Bezbradica, S. Gruber; I. Taniuchi

Row 2: J. Kisielow, S. Storck; S. Pierce, L. Miller; E. Starosvetsky

Row 3: Symposium picnic at the beach.

Row 4: R. Grosschedl, A. Weiss; K. Murphy, P. Gearhart; R. Ahmed, K. Rajewsky; G. Natoli, A. Rudenskyx




Row 1: J. Trinath, D. Mathis; B. Salomon, L. Graca; I. Weissman, B. Stillman

Row 2: W. Paul, Z. Ben-Sasson; C. Bliss, A. Doedee; T. Mak, S. Ghosh

Row 3: Blackford lawn

Row 4: H. von Boehmer, H. Ploegh; H. Qi, C. Vinuesa; L. Pasman, J. Bezbradica xi




Row 1: P. Budzynska; K. Dumstrei, H. Wardemann; D. Chen

Row 2: M. Busslinger, J. Skok, C. Murre; S. Trifari, A. Chang, S. Pope, A.-J. Tong, T. Arenzana

Row 3: D. Littman, A. O’Garra; F. Kurschus, R. Obst; S. Cemerski

Row 4: D. Cantrell, C. Rada; M. Smith; H. Bolton, A. Tanaka; A. Chawla, S. Tripathixii




Row 1: U. Weiss, R. Ahmed; T. Cohen, R. Newman; poster session in historic Bush Auditorium; J. Allison, S. Hedrick

Row 2: N. Srinivasan, U. Govender; C. Barthels, P. Rauf

Row 3: R. Medzhitov, Y. Belkaid; S. Nedospasov, A. Poltorak; E. Starosvetsky, D. Banerjee

Row 4: P. Gearhart, H. Singh, A. Chawla, F. Zhao; R. Locksley, A. Bendelac xiii




Row 1: L. Ramakrishnan; G. Natoli, S. Smale; F. Wermeling

Row 2: The Double Helix Jumpers; U. Basu, A. Kenter

Row 3: M.-W. Dobenecker; P. Bjorkman, E. Ghosn; A. Weiss, R. Flavell

xiv




Foreword

The Cold Spring Harbor Symposia on Quantitative Biology bring together scientists from all over the

world to present and evaluate new data and ideas in rapidly moving areas of biological research. Each year, a

topic is chosen that appears to be at a stage where general and intensive scrutiny and review is needed. There

are numerous criteria for selection of topics, including the rate of progress in a given field, how recent

research is highlighting connections among fundamental biological mechanisms, and the potential applica-

tions of the new discoveries to human health and disease. Cold Spring Harbor Laboratory selected the theme

of Immunity and Tolerance for the historic 78th Symposium in the series. Previous Symposia that have

included significant aspects of immunology have occurred on a roughly 10-year cycle, notably but not

limited to Antibodies (1967), Origins of Lymphocyte Diversity (1976), Immunological Recognition

(1989), and Signaling and Gene Expression in the Immune System (1999).

The immune system evolved to defend individuals against invading pathogens. However, because exag-

gerated responses to pathogens or commensals can result in damage to the host, mechanisms of immune

regulation have developed to inhibit pathology. These mechanisms also inhibit the immune response to self-

antigens and so prevent autoimmune disease. Advanced molecular techniques to perturb gene function in

experimental mouse models as well as the identification of genetic mutations in human diseases have

provided conclusive evidence toward the role of particular molecules and pathways in vivo, in the develop-

ment and function of the immune system. The genomic era has contributed to significant advances in our

understanding of mechanisms underlying human disease. During the past decades, immunology research was

revolutionized by the rapid identification of molecules, pathways, and cells contributing to innate and

adaptive immune responses. In addition, this has furthered our understanding of how failures in immuno-

regulation during immune responses to pathogens, commensals, or self can result in disease and inaugurated

the era of biologics as therapeutic agents. Major advances have been made toward our understanding of the

regulatory mechanisms in place to prevent inflammatory and autoimmune diseases. In turn, immunologists

and clinicians are attempting to exploit this knowledge to harness these pathways in order to eradicate cancer.

The decision to focus the 2013 Symposium on immunity and tolerance reflected the enormous research

progress achieved in recent years. The plan was to provide a broad synthesis of the current state of the field,

setting the stage for future discoveries and application and to introduce research topics on mechanisms of

human disease, extending beyond the more basic molecular research of past years. The Symposium spanned

a broad range of areas of investigation, including molecular mechanisms of B and T lymphocyte develop-

ment in experimental models, at levels ranging from the single cell to the entire organism and from single

genes to genomes. There was a good cover of development and function of innate cells, including myeloid

cells, NK (natural killer) cells, and a more recently defined innate lymphoid cell (ILC) that resembles T cells

in producing effector molecules such as cytokines but lacks an antigen receptor and has an early role like

other innate cells in the immune response. In keeping with Cold Spring Harbor tradition, the program

included talks on in-depth molecular mechanisms of transcriptional regulation of key immune pathways

in innate and adaptive cells of the immune system. Emerging areas of research were also covered, including

how metabolic pathways affect immune responses and, conversely, how immune cells may affect cell and

tissue physiology outside of the immune response and how commensal bacteria can affect the immune

response contributing to protection against pathogens or disease. Introduced were diverse immune mecha-

nisms underlying the events leading to chronic infection or immune control in HIV and tuberculosis, in

addition to mechanisms underlying autoimmune diseases that have promise to lead to new clinical therapies.

In arranging the Symposium, immunologists interacted with Cold Spring Harbor organizers to introduce

more on the mechanisms of the immune response underlying human disease. Opening night speakers

included James Allison, Jean-Laurent Casanova, Fiona Powrie, and Anjana Rao. Of special excitement

with respect to human disease was the progress that Jim Allison presented on “Immune Checkpoint Blockade

in Cancer Therapy,” having advanced this area by combining findings from experimental models and human

disease to expedite treatments of cancer. Hidde Ploegh delivered a compelling Dorcas Cummings lecture on

“The Logic of Your Immune System” to Laboratory friends, neighbors, and Symposium participants in

advance of the annual dinner parties.

This Symposium was attended by almost 385 scientists from more than 20 countries, and the program

included 67 invited presentations and 200 poster presentations. To disseminate the latest results and dis-

xv




cussion of the Symposium to a wider audience, attendees were able to share many of the Symposium talks

with their colleagues, whom were unable to attend, using the Leading Strand video archive, and interviews by

Laurie Dempsey, Karin Dumstrel, John Inglis, Richard Sever, Liz Thompson, and Jan Witkowski with

leading experts in the field were arranged during the Symposium and distributed as free video from the

Cold Spring Harbor Symposium interviews web site.

We thank Val Pakaluk, Mary Smith, Ed Campodonico, and his staff, in the Meetings & Courses Program

for their assistance in organizing and running the Symposium, and John Inglis and his staff at Cold Spring

Harbor Laboratory Press, particularly Jan Argentine, Inez Sialiano, and Rena Springer. Funds to support this

meeting were obtained from the National Institute of Allergy and Infectious Diseases, a branch of the

National Institutes of Health. Financial support from the corporate sponsors of our meetings program is

essential for these Symposia to remain a success and we are most grateful for their continued support.

Michel Nussenzweig

Anne O’Garra

Stephen Smale

David Stewart

Bruce Stillman

FOREWORDxvi




Sponsors

Contributions from the following companies provide core support for the Cold Spring Harbor meetings

program.

Corporate Benefactor

Astellas-OSI Oncology

Corporate Sponsors

Agilent Technologies

Bristol-Myers Squibb Company

Genentech, Inc.

GlaxoSmithKline

Life Technologies (Invitrogen & Applied Biosystems)

New England BioLabs, Inc.

Sanofi US

Plant Corporate Associates

Monsanto Company

Pioneer Hi-Bred International, Inc.

Foundation

Alpha-Hudson Institute for Biotechnology

xvii




Contents

Symposium Participants v

Foreword xv

Development and Antigen Receptor Gene Assembly

TET Proteins and 5-Methylcytosine Oxidation in the Immune System Ageliki Tsagaratou and

Anjana Rao 1

Control of Antigen Receptor Diversity through Spatial Regulation of V(D)J

Recombination Anja Ebert, Jasna Medvedovic, Hiromi Tagoh, Tanja A. Schwickert,

and Meinrad Busslinger 11

Establishment and Maintenance of B Cell Identity Rudolf Grosschedl 23

Transcriptional Establishment of Cell-Type Identity: Dynamics and Causal Mechanisms of T-Cell

Lineage Commitment Ellen V. Rothenberg, Ameya Champhekar, Sagar Damle, Marissa

Morales Del Real, Hao Yuan Kueh, Long Li, and Mary A. Yui 31

The Epigenetics of Early Lymphocyte Development C. Murre 43

Gene Regulation

Regnase-1, a Ribonuclease Involved in the Regulation of Immune Responses Shizuo Akira 51

Toward an Understanding of the Gene-Specific and Global Logic of Inducible Gene Transcrip-

tion Stephen T. Smale, Scott E. Plevy, Amy S. Weinmann, Liang Zhou, Vladimir R. Ramirez-

Carrozzi, Scott D. Pope, Dev M. Bhatt, and Ann-Jay Tong 61

Tolerization of Inflammatory Gene Expression John J. Seeley and Sankar Ghosh 69

The “Histone Mimicry” by Pathogens Uwe Schaefer, Jessica S.Y. Ho, Rab K. Prinjha, and

Alexander Tarakhovsky 81

Development and Function of Myeloid Subsets

Myb-Independent Macrophages: A Family of Cells That Develops with Their Tissue of Residence

and Is Involved in Its Homeostasis Elisa Gomez Perdiguero and Frederic Geissmann 91

The Molecular Choreography of IRF4 and IRF8 with Immune System Partners Harinder Singh,

Elke Glasmacher, Abraham B. Chang, and Bryan Vander Lugt 101

The IRF Family Transcription Factors at the Interface of Innate and Adaptive Immune

Responses Hiroaki Ikushima, Hideo Negishi, and Tadatsugu Taniguchi 105

T-Cell Differentiation and Function

IL-1b Strikingly Enhances Antigen-Driven CD4 and CD8 T-Cell Responses S.Z. Ben-Sasson,K. Wang, J. Cohen, and W.E. Paul 117

A Modified Model of T-Cell Differentiation Based on mTOR Activity and Metabolism

Jonathan D. Powell, Emily B. Heikamp, Kristen N. Pollizzi, and Adam T. Waickman 125

Novel Tools to Dissect the Dynamic Regulation of TCR Signaling by the Kinase Csk and the

Phosphatase CD45 Ying Xim Tan, Julie Zikherman, and Arthur Weiss 131

NK Cells and Innate Lymphoid Cells

Dissection of Signaling in Inflammation: Three Novel Inflammatory Regulators Thorsten

Berger, Mary E. Saunders, and Tak W. Mak 141

Tissue-Resident Natural Killer Cells Wayne M. Yokoyama, Dorothy K. Sojka, Hui Peng, and

Zhigang Tian 149

xix




Microbial Immunity

Immunology Taught by Human Genetics Jean-Laurent Casanova, Laurent Abel, and Lluis

Quintana-Murci 157

Systems Approach to Understand the Immune Response in Tuberculosis: An Iterative Process

between Mouse Models and Human Disease Anne O’Garra 173

The Zebrafish Guide to Tuberculosis Immunity and Treatment Lalita Ramakrishnan 179

Microbiota: Host Interactions in Mucosal Homeostasis and Systemic Autoimmunity Randy S.

Longman, Yi Yang, Gretchen E. Diehl, Sangwon V. Kim, and Dan R. Littman 193

The Promised Land of Human Immunology Laura F. Su, Arnold Han, Helen M. McGuire, David

Furman, Evan W. Newell, and Mark M. Davis 203

Tolerance, TREGS and Inflammasome

Transcriptional Control of Regulatory T-Cell Differentiation Joris van der Veeken, Aaron Arvey,

and Alexander Rudensky 215

miR-181 and Metabolic Regulation in the Immune System Adam Williams, Jorge Henao-Mejia,

Christian C.D. Harman, and Richard A. Flavell 223

Encoding Immunological Memory in the Initiation of B-Cell Receptor Signaling Susan K.

Pierce and Wanli Liu 231

Tumor Immunology and Genome Stability

Programmed Cell Death 1-Directed Immunotherapy for Enhancing T-Cell Function Koichi

Araki, Ben Youngblood, and Rafi Ahmed 239

Immune Surveillance of Unhealthy Cells by Natural Killer Cells Alexandre Iannello and David

H. Raulet 249

Studying Epstein–Barr Virus Pathologies and Immune Surveillance by Reconstructing EBV

Infection in Mice Tomoharu Yasuda, Tristan Wirtz, Baochun Zhang, Thomas Wunderlich,

Marc Schmidt-Supprian, Thomas Sommermann, and Klaus Rajewsky 259

Closing Lecture

Pathogen-Sensing, Regulatory T Cells, and Responsiveness-Tuning Collectively Regulate

Foreign- and Self-Antigen Mediated T-Cell Responses William E. Paul, Joshua D. Milner,

and Zvi Grossman 265

Author Index 277

Subject Index 279

CONTENTSxx




COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME … · 2014. 7. 17. ·...

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